Optical-Thermal Response of Laser-Irradiated Tissue (eBook)

Preface 4
Acknowledgement 5
Contents 6
Contributors 8
Part I Tissue Optics 11
1 Overview of Optical and Thermal Laser-Tissue Interaction and Nomenclature 12
1.1 Introduction 12
1.2 Notation 15
1.3 Format of Book 19
References 20
2 Basic Interactions of Light with Tissue 21
2.1 Introduction 21
2.2 Light 22
2.3 Characteristics of the Incident Light and the Irradiated Material 23
2.3.1 Remission 24
2.3.2 Scattering 27
2.3.3 Absorption and the Fate of Absorbed Energy 30
2.4 Summary 34
References 34
3 Definitions and Overview of Tissue Optics 35
3.1 Introduction to Tissue Optics 35
3.1.1 First Task of Tissue Optics 37
3.1.2 Second Task of Tissue Optics 38
3.2 Definitions and Geometry 38
3.2.1 Optical Properties 39
3.2.2 Optical Parameters 40
3.2.2.1 Photon Density, N0(r) 40
3.2.2.2 Radiance L(r,ˆs) 41
3.2.2.3 Fluence Rate f(r) 42
3.2.2.4 Net Flux Vector F(r) 43
3.2.2.5 Radiant Power (Radiant Energy Flux) and Radiant Energy 43
3.2.2.6 Radiant Exitance (Emittance) 43
3.2.2.7 Radiant Energy Density 44
3.2.2.8 Radiant Intensity 44
3.2.2.9 Irradiance 44
3.2.2.10 Radiant Exposure 45
3.2.2.11 Source Term S(r) 45
3.3 Reflection and Transmission at a Surface 45
3.3.1 Example: Reflection in Fiber Optics 47
3.3.2 Backscatter 48
3.3.3 Reflection of Diffuse Light 49
3.4 Propagation of Light into Tissue 50
3.4.1 Propagation of Collimated Light 50
3.4.1.1 Penetration Depth, d 51
3.4.1.2 Optical Depth (OD) 51
3.4.1.3 Albedo, a 51
3.4.1.4 Attenuation of Collimated Light 52
3.4.2 Propagation of Scattered Light 54
3.4.3 Transport Equation 55
3.4.3.1 Phase Function of Scattering 56
3.4.3.2 Phase Functions 58
3.4.4 Rate of Volumetric Absorption of Photon Energy Relation Between F(r) and
3.4.5 Penetration of Light in Tissue 61
3.5 Photon Sources and Detection 62
3.5.1 Sources 62
3.5.1.1 Collimated 62
3.5.1.2 Diffuse Sources 63
3.5.1.3 Point Source 64
3.5.2 Detection 65
3.5.3 Measurement of Fluence Rate 67
3.6 Summary 68
Appendix 70
Solid Angles 70
References 71
4 Polarized Light: Electrodynamic Fundamentals 73
4.1 Introduction 73
4.2 Light as Electromagnetic Wave 74
4.2.1 Maxwell Equations 74
4.2.2 Plane Waves in Homogeneous Media 76
4.2.2.1 Anisotropic Media 79
4.2.2.2 Chiral Media 81
4.2.3 Beyond Plane Waves 82
4.2.3.1 Beam-Waves and Their Properties 82
4.2.3.2 The Two Regimes: Quasi-Plane Waves and Quasi-Spherical Waves 84
4.2.3.3 Light Sources, Dipole Fields 86
4.3 Manipulating Polarization 88
4.3.1 Linear and Circular Polarization 88
4.3.2 Basic Hardware Elements 89
4.3.2.1 Retarder Plate 89
4.3.2.2 Linear Polarizer 91
4.3.3 Jones Formalism 92
4.3.4 Optical Elements in Jones Language 93
4.3.4.1 Projecting Filters 93
4.3.4.2 Transformers 94
4.3.4.3 Producing Circular Polarization 95
4.3.4.4 Blocking and Filtering Circular Polarization 96
4.3.5 Deflectors 97
4.3.5.1 Snellius and Fresnel Laws in Jones Language 98
4.4 Measuring Polarization 100
4.4.1 Basic Concepts 100
4.4.2 Time Averaging, Stokes Parameters 102
4.4.3 General Experiment Design, Coherence Matrix 103
4.4.4 Stokes Vectors 105
4.5 Beam Filters and Beam States 105
4.5.1 Mathematical Representation of Beam Filters 106
4.5.2 Virtual Beams as Base Vectors 109
4.6 Polarization Analysis of an Unknown Optical System 110
4.6.1 Designing the Experiment, from Jones to Perrin-Mueller Matrix 110
4.6.2 Interpreting the Perrin-Mueller Matrix, Alternative Codings 112
4.6.3 Mueller Versus Jones 113
References 115
5 Monte Carlo Modeling of Light Transport in Tissue (Steady State and Time of Flight) 117
5.1 Introduction 117
5.2 Basic Monte Carlo Sampling 119
5.2.1 Predicting the Step Size of a Photon 119
5.2.2 Predicting the Photon Launch Point for a Circular Flat-Field Beam 121
5.3 The Steady-State Monte Carlo Propagation of Photons in a Tissue 123
5.3.1 The Input File 123
5.3.2 Launching Photons 126
5.3.2.1 Collimated Launch 127
5.3.2.2 Isotropic Point Source 127
5.3.2.3 Collimated Gaussian Beam 128
5.3.2.4 Focused Gaussian Beam 129
5.3.3 Hop 130
5.3.3.1 Standard Hop 130
5.3.3.2 Check Boundaries 130
5.3.4 Drop 132
5.3.5 Spin 133
5.3.6 Terminate? 135
5.3.7 Normalizing Results for Output 136
5.4 Time Resolved Monte Carlo Propagation 137
5.5 Converting Time-Resolved Results to Frequency-Domain 141
5.6 Summary 143
5.7 Appendix: mc321.c 143
References 151
6 Diffusion Theory of Light Transport 153
6.1 Introduction 153
6.2 Simple Derivation of Diffusion Theory 154
6.2.1 Fick's Law 154
6.2.2 Energy Conservation and the Diffusion Equation 155
6.2.3 Relationships Between Hemispherical Fluxes, Radiance and Fluence Rate 155
6.2.4 Solution of the Source Free Diffusion Equation in a Simple Geometry 158
6.2.5 Boundary Conditions 159
6.2.6 Discussion 160
6.3 Diffusion Approximation in Transport Theory 160
6.3.1 Introduction 160
6.3.2 Transport Equation 161
6.3.3 Separation of Scattered from Non-scattered Light The Source Term
6.3.4 Diffusion Theory Derived from the Transport Equation 163
6.3.5 Validity of the Diffusion Approximation 165
6.3.6 Validity of the Eddington Approximation 166
6.3.7 Phase Functions 167
6.3.7.1 The ''Delta-Eddington'' Approximation 167
6.3.7.2 How Delta-Eddington Approximates the Henyey-Greenstein Function 169
6.3.8 Boundary Conditions Between Two Media, One Without and One with Scattering 170
6.3.8.1 Boundary Conditions for the Diffusion Equation 171
6.3.8.2 Boundary Conditions as Reflection Factors for Hemispherical Fluxes 171
6.3.8.3 A Useful Transformation When Boundary Conditions are Expressed in Terms of Reflection Factors 175
6.3.9 Boundary Conditions Between Two Media, Both with Scattering 176
6.4 Diffusion Theory in Simple Geometries 179
6.4.1 Plane Geometry 179
6.4.1.1 Measurable Quantities: Fluence Rate, Absorbed Energy, Reflection and Transmission 179
6.4.1.2 Infinitely Wide Slab of Finite Thickness with Wide-Beam Collimated Irradiance and Refractive Index Matched Boundaries 180
6.4.1.3 Semi-Infinite Medium with Wide Beam Collimated Irradiance and Refractive Index Mismatched Boundaries 182
6.4.1.4 Infinitely Wide Slab of Finite Thickness with Wide-Beam Diffuse Irradiance and Refractive Index Matched Boundaries 184
6.4.1.5 Kubelka-Munk 185
6.4.1.6 Semi-Infinite Medium with Wide-Beam Diffuse Irradiance and Refractive Index Mismatched Boundaries 185
6.4.2 Spherical Geometry with Isotropic Point Source 187
6.4.2.1 Equations and Solution 187
6.4.2.2 Boundary Conditions for the Spherical Geometry 189
6.4.2.3 Approximate Solutions for r2.8 189
6.4.3 Cylindrical Geometry 192
6.4.3.1 Linear Light Source as a Sum of Isotropic Point Sources 192
6.4.3.2 Fluence Rate About a Linear Light Source from the Diffusion Equations 193
6.4.4 Spatially Resolved Reflection and Fluence Rate Using the Diffusion Dipole Model 194
6.4.4.1 Diffusion Dipole Model 195
6.4.4.2 Boundary Condition and Solution 196
6.4.4.3 Wide Beam Collimated Irradiance and the Condition for 198
6.4.4.4 Reflectance in the Single Point Source Model 200
6.4.4.5 Pencil Beam as a Continuous Line of Point Sources 201
6.4.4.6 Discussion 203
6.5 Summary and Conclusion 204
Appendix 1: Delta Functions 206
Appendix 2: Legendre Polynomials 206
References 208
7 From Electrodynamics to Monte Carlo Simulations 210
7.1 Basic Scattering Concepts, Born Approximation 210
7.1.1 Scattering Geometry 211
7.1.2 Transition Matrix 212
7.1.3 Matrix Elements 214
7.1.4 Amplitude Scattering Matrix 216
7.1.5 Scattering Signal, Cross-Sections and Phase Function 217
7.1.6 Rayleigh Scatterer 220
7.2 Scattering from Interacting Rayleigh Particles 223
7.2.1 Scattering and Fluctuations 225
7.2.2 Forward Scattering, Extinction and Scattering Coefficient 228
7.2.2.1 Scattering Coefficient and Scattering Cross-Section 231
7.2.3 From Dilute Gas to Continuum and Back to Born Approximation 233
7.3 Scattering from Biological Tissues 234
7.3.1 Scattering from Particulate Systems 234
7.3.1.1 RDGB-Scattering 235
7.3.1.2 Interpreting form Factors 237
7.3.1.3 On the Applicability of the RDGB-Approximation 239
7.3.2 Scattering from a Continuum 240
7.3.2.1 Quasi-Particles 243
7.3.3 Scattering Matrices of Fluctuating Continuum 243
7.3.4 Modeling the Tissue Structure Factor 245
7.4 Multiple Scattering 248
7.4.1 Radiative Transfer 249
7.4.2 Photon Random Flight and Monte Carlo Simulations 254
7.5 Modeling Light Propagation as Polarized Random Flight 255
7.5.1 Photon Path 255
7.5.2 Initial Photon State, Launching a Photon 258
7.5.3 Scattered Photon States, Beams and Paths 258
7.5.4 Averages and Correlations 260
7.5.5 Polarized Segment Amplitude and Probability 262
7.5.5.1 Propagation 263
7.5.5.2 Scattering 264
7.5.5.3 Segment Probability 265
7.5.6 Detecting a Photon 266
7.5.7 From Path Probabilities to Monte Carlo 269
References 271
8 Measurement of Ex Vivo and In Vivo Tissue Optical Properties: Methods and Theories 274
8.1 Introduction 274
8.2 Photometric Techniques 275
8.2.1 Ex Vivo Methods 275
8.2.1.1 Direct Measurements in Optically Thin Tissue Sections 275
8.2.1.2 Indirect Measurements in Optically Thick Tissue Sections 280
8.2.1.3 Indirect Measurements in Bulk Tissue 283
8.2.2 In Vivo Methods 285
8.2.2.1 Total Steady-State Diffuse Reflectance 286
8.2.2.2 Spatially-Resolved, Steady-State Diffuse Reflectance 293
8.2.2.3 Spectrally-Constrained, Steady-State Diffuse Reflectance 298
8.2.2.4 Time-Resolved and Frequency-Domain Diffuse Reflectance 302
8.2.2.5 Interstitial Fluence Rate and Radiance 309
8.2.2.6 Diffuse Optical Tomography 311
8.3 Photothermal Techniques 313
8.3.1 Pulsed Photothermal Radiometry 313
8.3.2 Photoacoustic Spectroscopy 317
8.4 Summary and Conclusions 320
References 321
9 Dynamic Changes in Optical Properties 327
9.1 Introduction 327
9.2 Shift in Absorption Resonance with Temperature 327
9.2.1 Water 328
9.2.2 Deoxyhemoglobin and Oxyhemoglobin 330
9.3 Thermal Lensing 333
9.4 Photothermal Conversion of Oxyhemoglobin to Methemoglobin 335
9.4.1 Combined Bathochromic Shift and metHb Formation 337
9.5 Protein Denaturation 339
9.5.1 Tissue Denaturation and Feedback 339
9.5.2 Red Blood Cell Membrane Protein Denaturation 339
9.5.3 Modeling of Laser Treatment During Denaturation 340
9.6 Change in Water Content 342
9.6.1 Evaporation 342
9.6.2 Pressure 343
9.6.3 Replacement of Water with Biocompatible Fluid 344
9.7 Optical Clearing Agents 344
9.8 Conclusion 350
References 351
Part II Thermal Interactions 356
10 Laser Generated Heat Transfer 357
10.1 Background and Rationale 357
10.2 Heat Transfer Fundamentals 358
10.2.1 Energy Conservation Principles 358
10.2.2 Conduction Processes 360
10.2.3 Convection Processes (Case B) 365
10.2.3.1 Interior Forced Convection Correlations 0 For Flow Through a Circular Conduit of Diameter, D , and Length, L 372
10.2.3.2 Exterior Forced Convection Correlations 374
10.2.3.3 Free Convection Correlations 376
10.2.4 Specified Heat Flux (Radiation Processes) (Case C) 378
10.2.5 Insulated Surfaces (Case D) 388
10.2.6 Boundary Conditions at Material Interfaces 389
10.3 Bioheat Transfer with Blood Perfusion 390
10.4 Special Analyses of Bioheat Transfer Relating to Laser Irradiation of Tissue 391
10.4.1 Spray Cooling of the Skin Surface During Laser Irradiation 392
10.5 Comments and Conclusion 400
References 400
11 Temperature Measurements 402
11.1 Introduction 402
11.2 General Concepts 403
11.2.1 Classification of Temperature Transducers 403
11.2.1.1 Thermal Expansion 403
11.2.1.2 Boltzmann Factor 403
11.2.1.3 Seebeck Effect 404
11.2.1.4 Radiation 404
11.2.1.5 Phase Transitions 404
11.2.2 Transducer Specifications 405
11.2.2.1 Transducer Linearity 405
11.2.2.2 Transducer Sensitivity 405
11.2.2.3 Time Constant 406
11.2.2.4 Specificity 406
11.2.2.5 Transducer Impedance 406
11.2.3 Instrument Specifications 408
11.2.3.1 Accuracy 408
11.2.3.2 Resolution 408
11.2.3.3 Precision 409
11.2.3.4 Reproducibility or Repeatability 409
11.3 Thermistors 410
11.3.1 Basic Principles 410
11.3.2 Thermistor Instrumentation 411
11.4 Thermocouples 412
11.4.1 Thermocouple Construction 412
11.4.2 Thermocouple Physics 412
11.4.3 Thermocouple Characteristics 414
11.4.4 Analysis of Thermocouple-Specific Errors 415
11.4.4.1 Nonhomogeneous Wires 415
11.4.4.2 Cable Connections 415
11.4.4.3 Thermocouple Reference 416
11.5 Error Analysis of Probe-Based Transducers 417
11.5.1 Time Constant 417
11.5.1.1 Conduction-Dominated Time Constant 417
11.5.1.2 Convective Boundary Condition 419
11.5.1.3 Manufacturer Specifications 420
11.5.2 Measurement Errors in the Presence of Spatial Tissue Temperature Gradients 421
11.5.3 Surface Measurement Errors 424
11.5.4 Direct Absorption of External Energy into the Probe 424
11.6 Infrared Temperature Measurement 425
11.6.1 Electromagnetic Radiation Spectrum 425
11.6.2 Planck Radiation Law 426
11.6.3 Wide Band Radiation Heat Transfer 427
11.6.4 Band-Limited Radiation 427
11.6.5 Making a Black Body 428
11.6.6 Gray Bodies 430
11.6.7 Image Formation Effects 430
11.6.7.1 Optical Pathway Attenuation 431
11.6.7.2 Optical Axis Thermal Gradients 432
11.6.7.3 Image Spot Size Effects 434
11.6.8 Summary 436
11.7 Acoustic Measurements of Temperature 436
11.7.1 Ultrasound-Based Thermal Imaging 437
11.7.1.1 Ultrasound Imaging 437
11.7.1.2 Principles of Ultrasound-Based Thermal Imaging 437
11.7.1.3 Relationship Between Speed of Sound and Temperature 440
11.7.1.4 Illustration of Ultrasound-Based Thermal Imaging 441
11.7.1.5 Advantages and Limitations of Ultrasound-Based Thermal Imaging 445
11.7.2 Thermal Photoacoustic Imaging 447
11.7.2.1 Photoacoustic Imaging 447
11.7.2.2 Principles of Photoacoustic Thermal Imaging 447
11.7.2.3 Temperature Dependence of the Grueneisen Parameter 448
11.7.2.4 Illustration of Thermal Photoacoustic Imaging 451
11.7.2.5 Advantages and Limitations of Thermal Photoacoustic Imaging 453
11.7.3 Summary 453
References 454
12 Tissue Thermal Properties and Perfusion 457
12.1 Basic Definitions 457
12.1.1 Significance 457
12.1.2 Thermal Conductivity 458
12.1.3 Thermal Diffusivity 458
12.1.4 Specific Heat 460
12.1.5 Tissue Perfusion 461
12.1.6 Reviews of Thermal Measurements 462
12.2 Measurement of Thermal Properties 462
12.2.1 Overview 462
12.2.2 Constant Temperature Heating Technique 463
12.2.3 Probe Design 467
12.2.4 Calibration 468
12.3 Temperature Dependent Thermal Properties 469
12.3.1 Temperature Dependence of Organ Tissue 469
12.3.2 Temperature Dependence of Human Arterial Tissue 470
12.3.3 Temperature Dependence of Canine Arterial Tissue 471
12.3.4 Temperature Dependence of Swine Myocardial Tissue 472
12.3.5 Thermal Properties of Frozen Tissue 473
12.4 Thermal Properties as a Function of Water and Fat Content 473
12.5 Measurements of Perfusion 474
12.5.1 Introduction 474
12.5.2 Alcohol-Fixed Canine Kidney Experiments 475
12.5.3 Canine Muscle Experiments 476
12.5.4 Trauma at Insertion Site will Decouple Probe from Tissue 477
12.5.5 Temperature Dependence of Perfusion 477
12.6 Conclusions 481
Appendix 1: Thermal Standards 482
Appendix 2: Perfusion Values 483
References 486
13 Thermal Damage and Rate Processes in Biologic Tissues 488
13.1 Introduction 488
13.2 Pathophysiology and Pathogenesis of Photothermal Lesions 489
13.2.1 General Principles 489
13.2.1.1 Primary Thermal Injury 489
13.2.1.2 Secondary (Delayed) Thermal Injury 489
13.2.1.3 Identification of Thermal Lesions 489
13.2.1.4 Factors Associated with Thermal Lesion Size, Development and Progression 491
13.2.1.5 Cells: Basic Units of Life and Death 492
13.2.2 Zones of Thermal Damage: Gross and Histologic Pathologic Features 492
13.2.2.1 Heat Source Volumes and Thermal Gradients 492
13.2.2.2 Ex Vivo and In Vivo Heating: No Survival 494
13.2.2.3 In Vivo Heating with Short Term Survival 494
13.2.2.4 In Vivo Heating with Prolonged Survival 494
13.2.3 Mechanisms of Thermal Injury 496
13.2.3.1 Primary (Direct) Thermal Injury 496
13.2.3.2 Tissue Mass Ablation 497
13.2.3.3 Carbon Formation and Carmelization of Tissue 498
13.2.3.4 Water Vaporization 499
13.2.3.5 Thermal Protein Denaturation (Thermal Protein Coagulation) 499
13.2.3.6 Thermal Denaturation of Proteins 501
13.2.3.7 Heating of Cellular Membranes 501
13.2.4 Mechanisms of Heat-Induced Cell Death 502
13.2.4.1 ''Heat Sensitive'' and ''Heat Resistant'' Cells and Tissues 502
13.2.4.2 Minimal Thermal Injury that Leads to Cell Death 502
13.2.4.3 Post-Mortem Necrosis 503
13.2.4.4 Cell Death Due to Rapid Thermal Coagulation (Heat Fixation) 505
13.2.4.5 Heat Fixation Vs. Pathophysiologic Post-Mortem Coagulation Necrosis: A Diagnostic Conundrum 506
13.2.4.6 Programmed Cell Death (Apoptosis) 506
13.2.5 Wound Healing 507
13.2.5.1 Organization 507
13.2.5.2 Tissue Regeneration and Tissue Repair 507
13.2.5.3 Granulation Tissue and Scar Formation 509
13.2.6 Role of Heat Shock Proteins (HSP) in Thermal Lesions 509
13.2.7 Mathematical Modeling of Pathophysiologic Thermal Effects 509
13.3 Thermodynamics and Kinetics of Thermal Damage Processes 511
13.3.1 Foundations of Thermal Analysis 511
13.3.1.1 Thermal Energy and Enthalpy 512
13.3.1.2 Entropy: The Second Law of Thermodynamics 515
13.3.2 Modeling Tissue Thermal Events 520
13.3.2.1 Sub-Coagulation Thermal Models 520
13.3.2.2 Evaporation of Surface Water 520
13.3.2.3 Water Vaporization 521
13.3.2.4 Coagulation Processes 526
13.3.3 Kinetics of Thermal Damage Processes 527
13.3.3.1 Theoretical Foundations 527
13.3.3.2 Experimental Determination of Rate Process Coefficients 534
13.4 Summary 545
References 545
14 Pulsed Laser Ablation of Soft Biological Tissues 551
14.1 Introduction 551
14.2 Tissue Properties Relevant for Ablation 551
14.3 Linear Thermo-Mechanical Response to Pulsed Irradiation 556
14.4 Thermodynamics and Kinetics of Phase Transitions 559
14.4.1 Phase Diagrams 559
14.4.2 Surface Vaporization 560
14.4.3 Normal Boiling 561
14.4.4 Phase Explosion and Explosive Boiling 562
14.4.5 Effects of the Tissue Matrix on the Phase Transitions 565
14.4.6 Vapor Explosion and Photothermal Dissociation of the Tissue Matrix 566
14.4.7 Effect of Stress Confinement on the Ablation Process 567
14.5 Photochemical Decomposition 569
14.6 Ablation Plume Dynamics 571
14.6.1 Primary Material Ejection in Nanosecond Ablation 572
14.6.2 Primary Material Ejection in Microsecond Ablation 577
14.6.3 Recoil Stress and Secondary Material Ejection 580
14.6.4 Shielding and Flow-Induced Material Redeposition 584
14.7 Ablation Models and Metrics 585
14.7.1 Ablation Metrics 586
14.7.2 Heuristic Models 587
14.7.3 Mechanistic Models 590
14.7.4 Molecular Dynamics Simulations 592
14.8 UV and IR Ablation 593
14.9 Ablation in a Liquid Environment 598
14.10 Control of Ablated Mass and Thermal and Mechanical Side Effects 603
14.11 Outlook and Challenges 604
References 606
15 Pulsed Laser Tissue Interaction 616
15.1 Introduction 616
15.1.1 Pulsed Infrared Laser Ablation 618
15.1.2 Thermal Damage 619
15.1.3 Multiple Origins of Tissue Damage 619
15.2 General Design Considerations for IR Ablation 621
15.2.1 Wavelength Considerations 621
15.2.2 Pulse Duration Considerations 623
15.2.3 Energy or Power Density Considerations 624
15.2.3.1 First-Order Approximations 624
15.2.4 Spot Size Considerations 630
15.2.5 Repetition Rate Considerations 631
15.2.6 Spatial Beam Profile Considerations 633
15.2.7 Fluid Layer 634
15.3 The Effect of Dynamic Changes in Optical Absorption 635
15.3.1 The Moses Effect 636
15.3.2 IR Spectroscopy of Water 637
15.3.3 Modeling Dynamic Shifts in Absorption 640
15.3.4 The Dynamic UV Optical Properties of Tissue 642
15.3.5 Implications of UV and IR Dynamic Optical Properties 643
15.4 Summary 643
References 644
Part III Medical Applications 649
16 Introduction to Medical Applications 650
16.1 Introduction 650
16.2 Light Propagation in Tissue 651
16.2.1 Treatment 651
16.2.2 Diagnosis 653
16.3 Optical-Thermal Response 654
References 656
17 Optical Fiber Sensors for Biomedical Applications 657
17.1 Introduction 657
17.2 Optical Fiber Sensors 658
17.2.1 Basic System Design 658
17.2.2 Classification of Fiber Optic Sensors for Biomedicine 659
17.3 Fiber Fundamentals 662
17.3.1 Light Transmission 662
17.3.2 Fiber Classifications 663
17.3.3 Fiber Bending 666
17.3.4 Fiber Tip Geometries for Biomedical Sensors 666
17.3.4.1 Tapered Fiber Tips 667
17.3.4.2 Ball Shaped Fiber Tips 669
17.3.4.3 Side-Firing Tips 671
17.3.5 Fiber Tip Manufacturing 672
17.3.5.1 Biomedical Deployment 673
17.4 Fiber-Based White Light Spectroscopy 673
17.4.1 Reflectance Geometry 673
17.4.1.1 Conventional Reflectance Sensor Design 673
17.4.2 Depth Sensitivity 674
17.4.2.1 Steady-State Spectroscopy: Geometric Approaches 675
17.4.2.2 Polarization Reflectance Gating: Steady-State Spectroscopy 684
17.4.2.3 Time-Resolved Reflectance Spectroscopy 686
17.4.3 Interstitial Geometry 688
17.4.3.1 Fluence Sensors 688
17.4.3.2 Pre-Clinical and Clinical Applications 691
17.5 Fluorescence Spectroscopy Fibers 693
17.5.1 Basic Approach 693
17.5.2 Fluorescence Sensor Design 694
17.5.2.1 Single and Multi-Fiber Sensors: Pros and Cons 694
17.5.2.2 Effect of Spacer-Thickness 695
17.5.2.3 Fiber Diameter and Orientation 696
17.5.2.4 Effect of Illumination-Collection Fiber Separation 697
17.5.3 Influence of Tissue Optics 697
17.6 Optical Coherence Tomography Fibers 698
17.7 Raman Spectroscopy Fibers 700
17.7.1 Basic Approach 700
17.7.2 Raman Probe Design 700
17.8 Summary 704
References 705
18 Optical Coherence Tomography 709
18.1 Introduction 709
18.2 Coherence Gating 714
18.2.1 The Detector Current from a Michelson Interferometer 714
18.2.2 Time-Domain OCT 715
18.2.2.1 Signal Description 715
18.2.2.2 Sensitivity 717
18.2.2.3 Imaging 718
18.2.3 Spectrometer Based Fourier Domain OCT 720
18.2.3.1 Signal Description 720
18.2.3.2 Sensitivity 720
18.2.3.3 Imaging 722
18.2.4 Swept Source Based Fourier Domain OCT 722
18.2.4.1 Signal Description 722
18.2.4.2 Sensitivity 723
18.2.4.3 Imaging 723
18.3 Confocal Gating 724
18.3.1 PSF for a Point Reflector 726
18.3.2 PSF for Specular Reflection 726
18.3.3 PSF for Reflection from Backscattering 727
18.4 Quantitative Measurements of Optical Properties with OCT 728
18.4.1 The Optical Properties of (Bulk) Tissue 729
18.4.2 Single Backscattering 730
18.4.3 Backscattering and Multiple Forward Scattering 731
18.4.4 Quantitative Attenuation Coefficient Measurements 733
18.4.5 Clinical Implications 733
References 736
19 Photoacoustic Tomography 738
19.1 Introduction 738
19.2 Initial Photoacoustic Pressure 739
19.3 Photoacoustic Equation 741
19.4 Forward Solution 741
19.5 Dark-Field Confocal Photoacoustic Microscopy 744
19.6 Reconstruction-Based Photoacoustic Tomography 750
References 753
20 Steady State Fluorescence Spectroscopy for Medical Diagnosis 756
20.1 Introduction 756
20.2 Optical Spectroscopy 756
20.3 What is Fluorescence? 758
20.4 Fluorescence Spectroscopy 759
20.5 Properties of Fluorescence 761
20.5.1 Stokes' Shift 761
20.5.2 Emission Wavelength is Independent of the Excitation Wavelength 762
20.5.3 Mirror Image Rule 762
20.5.4 Fluorescence Lifetimes and Quantum Yield 762
20.6 What Fluoresces? 763
20.6.1 Natural Biological Fluorophores 763
20.6.2 Extrinsic Fluorophores 764
20.7 Quantitative Representation of Fluorescence 765
20.7.1 In a Dilute Solution 765
20.7.2 In a Concentrated Solution 766
20.7.3 Extracting Intrinsic Fluorescence 767
20.8 Instrumentation 770
20.8.1 Light Source 770
20.8.2 Wavelength Selector (Excitation) 771
20.8.3 Wavelength Dispersion (Emission) 771
20.8.4 Detector 771
20.8.5 Delivery 772
20.8.6 Spectral Imaging 773
20.8.6.1 Spectral Imaging Modalities 773
20.8.7 Spectroscopy Versus Imaging 777
20.8.8 Calibrating Your Spectra (Or Data Processing) 781
20.8.9 Data Analysis 782
20.9 Applications 784
References 786
21 Molecular Imaging Using Fluorescence and Bioluminescence to Reveal Tissue Response to Laser-Mediated Thermal Injury 794
21.1 Overview 794
21.2 In Vivo Bioluminescence Imaging (BLI) 795
21.2.1 Principles of In Vivo Bioluminescence Imaging 796
21.3 Recent Advances 798
21.3.1 Dual and Triple Reporter Genes 798
21.3.2 3D-Image Reconstruction 798
21.4 Fluorescence Imaging 800
21.4.1 New Fluorescent Proteins 802
21.5 Bioluminescent Imaging of Heat Shock Protein 70 with Laser Thermal Stress/Injury 802
21.5.1 In Vitro Imaging of hsp70-Luc-NIH-3T3 Cells Treated with a Ho:YAG Laser 803
21.5.2 In Vitro Imaging of Hsp70-Luc-Organotypic Raft Cultures Treated with a Carbon Dioxide Laser 804
21.5.3 In Vivo Imaging of Hsp70-Luc-FVB Mice Treated with a Carbon Dioxide Laser on the Skin and Organs 806
21.6 Photodynamic Therapy (PDT) 809
21.6.1 In Vivo Imaging of E. Coli-Luc Injected Balb/c Mice Treated with a 660 nm Diode Laser 809
21.7 Low-Level Laser Therapy (LLLT) 810
21.7.1 In Vivo Imaging of iNOS-Luc-FVB Mice Treated with a Four Channel Diode Laser 810
21.8 Recent Advances in Bioluminescent and Fluorescent Imaging 811
21.9 Conclusions 812
References 812
22 The Optics of Bruising 819
22.1 Introduction 819
22.2 Physiology 820
22.2.1 Chromophores, Biochemistry and Immunological Reaction 820
22.2.2 Temporal Development 822
22.2.2.1 Immediate Skin Reactions and Resulting Injury 822
22.2.2.2 Temporal Development of Bilirubin Concentration 823
22.2.2.3 The Central White Spot 825
22.2.2.4 Other Chromophores 825
22.3 The Physics of Minor Trauma 826
22.3.1 The Optics of Traumatic Injuries 826
22.3.1.1 Observation of Yellow Color, Perception and Shielding 827
22.3.1.2 Photobleaching of Bilirubin in Skin 828
22.3.1.3 Reflectance Spectra, Observed Bruise Color and Depth of the Injury 828
22.3.1.4 Color Coordinates 829
22.3.2 Biomechanical Modeling of Bruised Skin 830
22.3.3 Transport of Hemoglobin Species in Tissue by Convection and Diffusion 831
22.3.3.1 Transport of Hemoglobin in Dermis 834
22.3.3.2 Transport and Generation of Bilirubin in Dermis 836
22.3.3.3 Planar Skin Model 836
22.3.4 Photon Transport in Bruised Tissue 838
22.3.4.1 Analytic Photon Transport Model for Skin 839
22.4 Optical Identification and Characterization of Bruises 839
22.4.1 Reflection Spectroscopy 839
22.4.2 Hyperspectral Imaging 841
22.4.3 Post Mortem Bruises 842
22.4.4 Bruises in Living People 843
22.4.4.1 Bruises in Children 843
22.4.4.2 Bruises in Adults 845
22.4.4.3 Bruises in Elderly People 846
22.4.5 Age Determination of Bruises 848
22.5 The Future of the Optics of Bruises 849
References 850
23 Laser Treatment of Port Wine Stains 853
23.1 Introduction 853
23.1.1 Port Wine Stain (PWS) 853
23.1.2 PWS Therapy 854
23.1.3 Biological and Physical Endpoints of PWS Laser Therapy 857
23.2 Optical and Thermal Considerations in PWS Laser Therapy 858
23.2.1 Beam Diameter (Spot Size) 859
23.2.2 Wavelength 860
23.2.2.1 Absorption Selectivity 860
23.2.2.2 Optical Screening Within Individual Blood Vessels 862
23.2.2.3 Optical Interaction Between Nearby Vessels -- Shading 866
23.2.2.4 Clinical Experience 870
23.2.3 Pulse Duration 872
23.2.3.1 Thermal Relaxation Time of Blood Vessel as a Whole 872
23.2.3.2 Thermal Relaxation Times of Erythrocytes and Melanosomes 875
23.2.3.3 Heat Transport into the Vessel Wall 876
23.2.3.4 Interaction Between Thermal Relaxation and Optical Screening 877
23.2.3.5 Clinical Experience 879
23.2.4 Radiant Exposure 880
23.2.5 Active Cooling 880
23.2.5.1 Cryogen Spray Cooling 882
23.2.5.2 Contact Cooling and Chilled Air 883
23.2.5.3 Optimal Cooling Duration 885
23.2.5.4 Maximal Radiant Exposure Applicable with Dynamic Cooling 886
23.3 Beyond the Customary Paradigm 887
23.3.1 Sequential Application of Multiple Laser Pulses 887
23.3.1.1 Extended Pulse PDL and KTP Lasers 887
23.3.1.2 Multiple Laser Pulses with Multiple Cryogen Spurts 888
23.3.1.3 Multiple Passes of the Laser Beam 890
23.3.2 Dynamic Changes in Tissue Optical Properties During Laser Irradiation 891
23.3.3 Dual-Wavelength Irradiation 893
23.3.4 Optical Clearing 894
23.4 Outlook 895
23.4.1 Optimization of Laser Treatment Parameters on an Individual Patient Basis 895
23.4.1.1 Diffuse Reflectance Spectroscopy and Colorimetry 896
23.4.1.2 Novel Optical Techniques for PWS Characterization 897
23.4.2 Real-Time Guidance of Therapy Using Feedback Signals 898
23.4.3 Photodynamic Therapy 899
References 900
24 Infrared Nerve Stimulation: A Novel Therapeutic Laser Modality 908
24.1 Introduction 908
24.1.1 Limitations of Electrical Nerve Stimulation 909
24.1.2 Definition of Optical Stimulation 910
24.1.3 Previous Work in Optical Stimulation 910
24.2 Optical Stimulation in the Peripheral Nervous System (PNS) 910
24.2.1 Feasibility, Methodology, and Physiological Validity in the PNS 911
24.2.2 Threshold for Stimulation Dependence on Wavelength 915
24.2.3 Nerve Histological Analysis 918
24.2.4 Biophysical Mechanism 919
24.3 Other Applications 922
24.3.1 Sensory Nerve Stimulation -- Towards an Optically-Based Cochlear Implant 922
24.3.2 Optical Stimulation in the Central Nervous System (CNS) 923
24.4 Impact 927
24.4.1 Applications 927
24.4.2 Future Directions 928
References 929
25 Summary and Future 933
25.1 Photothermal Therapies 934
25.1.1 Ablative and Non-ablative Surgical Lasers 935
25.1.2 Selective Photothermolysis Using Endogenous Chromophores 935
25.1.3 Selective Photothermolysis Using Exogenous Particles or Dyes 936
25.1.4 Fractional Photothermolysis 937
25.2 Imaging, and Photothermal Treatments 938
25.3 Summary 938
Index 939